Energy Storage and Lipid Transport Flashcards
Glucose is the preferred fuel for tissues, but some have an absolute requirement, what are they?
RBCs, kidney medulla, lens of eye no neutrophils.
A stable blood glucose concentrations is essential for brain function, what is it usually and how far does it have to drop for death?
5mmol/L is usual and at 0.6mmol/L there will be brain damage/death.
The store of glucose/energy as glycogen:
It is stored as _________ in the ________ and ___________ muscle. It is a __________ consisting of chains of glucose residues, organised like branches of a tree around a diner of protein called ___________, which as as a ________.
Granules Liver Skeletal Polymer Glycogenin Primer
Glucose residues in glycogen are linked by what type of bond and why is there more than one?
Residues are linked by alpha-1,4-glycosidic bonds with alpha-1,6-glycosidic bonds at branch points every 8-10 residues. There are multiple sites for enzymes to act, meaning rapid release and reduced osmotic effect.
The first step in glycogenesis is: glucose + ATP–> _______________ + ____. This is catalysed by _________ in normal tissues and __________ in the liver.
Glucose-6-phosphate
ADP
Hexokinase
Glucokinase
After glucose –> G-6-P in glycogenesis, which enzyme changes it to G-1-P?
Phosphoglucomutase.
In the third step of glycogenesis, what must be added to G-1-P to convert it to UDP-glucose + PPi?
H2O and UDP.
The enzyme is G-1-P uridyl transferase.
How is UDP glucose incorporated into the glycogen chain, for its growth?
nGlycogen residues + UDP-glucose —> n+1 residues + UDP.
In the last step of glycogenesis, which enzymes are used to make a-1,4-glycosidic bonds and which for a-1,6?
Glycogen synthase is used for alpha-1,4 bonds and branching enzyme is used for alpha-1,6.
First step of glycogenolysis:
nGlycogen residues + __ —> n-1Glycogen residues + ________________. The enzymes used are __________ ___________ for breaking alpha-1,4 bonds and ____________ _________ for breaking alpha-1,6.
Pi
Glucose-1-phosphate
Glycogen dephosphorylase
Debranching enzyme
In the second step of glycogenolysis, which enzymes catalyses the conversion of G-1-P to G-6-P?
Phosphoglucomutase.
Why is glycogenesis not a simple reverse of glycogenolysis?
Different enzymes allow for simultaneous inhibition and stimulation of pathways.
What happens to the glucose-6-phosphate that’s been obtained from the glycogen in glycogenolysis?
In the muscle it feeds into glycolysis and used for energy production, while only in the liver can it be converted completely back into glucose, then released into the blood for use by other tissues.
The liver glycogen acts as a buffer for blood glucose levels, why must skeletal muscle have a differing function?
It lacks glucose-6-phosphatase.
What are the rate limiting enzymes of glycogenesis and glycogenolysis?
Glycogenesis - glycogen synthase and its reciprocal for
Glycogenolysis - glycogen phosphorylase.
They are controlled by hormones.
Which three hormones control the glycogen store in the liver and how?
Glucagon and Adrenaline phosphorylate the rate limiting enzymes of glycogenesis and glycogenolysis to decrease synthesis and phosphorylate the glycogen.
Insulin dephosphorylates the rate determining enzymes to decrease glycogen phosphorylase activity and increase glycogen synthase.
How does the control of skeletal muscle glycogen stores differ from that in the liver?
Glucagon has no effect on muscle glucagon stores, but AMP allosterically activates glycogen phosphorylase, which does not happen in the liver.
Glycogen storage diseases are inborn errors of metabolism. The arise from a ____________ or a dysfunction in enzymes of glycogen metabolism. There are 11 types, their incidence varies and the severity depends on the ________\________ affected. Excess glycogen storage leads to ________ damage and diminished leads to ______________ and poor __________ tolerance.
Deficiency Tissue/enzyme Tissue Hypoglycaemia Exercise
Give a couple of examples of glycogen storage diseases.
McArdle disease - muscle glycogen phosphorylase deficiency.
Von Gierke’s disease - glucose-6-phosphatase deficiency (leads to a large liver).
Gluconeogenesis is an alternative to glycogen as a source of glucose that is used when and where does it occur?
It occurs after 8 hours of fasting, where liver glycogen levels are depleted. It occurs in the liver (and kidney cortex).
What are the 3 main precursors to glucose in gluconeogenesis?
Lactate (anaerobic glycolysis of exercising muscle and RBCs - Cori cycle). Glycerol (from adipose TAG breakdown). Amino acids (mainly alanine).
Why is there no net synthesis of glucose from acetyl-CoA?
Pyruvate dehydrogenase is irreversible, explaining why acetyl-CoA isn’t a gluconeogenesis precursor.
In gluconeogenesis, there are 3 enzymes for steps where the reactions aren’t just simple glycolysis reversals, what are they and how are they regulated?
PEPCK (oxaloacetate to phosphoenolpyruvate), fructose-1,6-bisphosphatase (along with PEPCK at major control site) and glucose-6-phosphatase.
How are the 3 key enzymes of gluconeogenesis controlled?
Regulation of these enzymes is by hormones responding to starvation, prolonged exercise and stress.
Glucagon and Cortisol increase the amount of PEPCK and the level of activity of fructose-1,6-phosphatase to stimulate gluconeogenesis, whereas
Insulin decrease the amounts/ the activity of F-1,6-Pase to inhibit.
How does the tissue’s source of glucose change over time after having ingested food?
2 hours after feeding, glucose comes from the food and generally from 1-10 hours, there is also some from glycogenolysis. After 8-10 hours, glucose is sourced from gluconeogenesis.
When energy intake is excess of requirements, where is it stored and give a property of this molecule that dictates how it must be stored?
Lipid storage as triacylglycerol.
It is hydrophobic, so stored in an anhydrous form in specialised tissue (adipose).
Triacylglycerol storage/ mobilisation is under hormonal control and it is a highly efficient energy store, when is it utilised?
In pregnancy, exercise, stress and starvation.
Adipocytes have a large lipid _________ in the middle of the, (mainly TAG and ____________ _______), with the cytoplasm and _________ pushed to the edge. They’re typically ___mm in diameter and can _______ as mor fat is added. The average adult has ___kg of fat, with the adipocytes increasing x__ before ________ and increasing the total number.
Droplet Cholesterol ester Organelles 0.1 Expand 15 4 Dividing
